Identification of a Naturally Occurring Polymorphism in the Promoter Region of the Norepinephrine Transporter and Analysis in Major Depression

Abstract

Disturbances in the noradrenergic neurotransmission system have been implicated in the etiology of mood disorders. The norepinephrine transporter (NET) is a mainMonoamine neurotransmitters, particularly norepinephrine (NE) and serotonin play an important, possibly primary, role in pathophysiology and treatment of mood disorders. Many studies have reported altered NE levels in depressed patients (reviewed by Charney 1998). Studies of NE metabolites showed decreased urinary levels of MHPG (3-methoxy-4-hydroxyphenylglycol),

No Association of the G1287A Polymorphism in the Norepinephrine Transporter Gene and Susceptibility to Major Depressive Disorder in a Japanese Population

“…The present results replicated those by Owen et al, 7) Zill et al, 14) and Chang et al 15) in a Japanese population. The frequency of G/G genotype in patients with MDD was about 10% lower than that in healthy volunteers in this study though the statistical difference was not significant.…”

“…17) There is no association between any genotype and MDD in Caucasian populations 14) and Han Chinese. 15) As for NET G1287A polymorphism, the A allele frequency in Japanese healthy volunteers (23.5%) reported in this study was lower than that in previously reported Caucasian (33.1-33.5%), 7,14) and Han Chinese (35.7%) populations. 15) Although the large scale study should be done for confirmation, the A allele frequency of NET G1287A polymorphism may account for the ethnic difference in the susceptibility to MDD as well as NET T-182C polymorphism.…”

“…Several investigators have reported the relationship between the NET G1287A polymorphism and several psychiatric disorders including MDD, 7,14,15) schizophrenia, 8) alcohol dependence 10) and panic disorder 16) in Caucasian and Han Chinese populations, and none of them showed significant relationship. The present results replicated those by Owen et al, 7) Zill et al, 14) and Chang et al 15) in a Japanese population.…”

Association between Norepinephrine Transporter Gene Polymorphism and Major Depression

“…The NET gene is located on chromosome 16q12.2, which spans approximately 45 kb and consists of 14 exons [12]. Recently, the T → C point mutation 182 upstream of the first codon in the 5) flanking promoter region of the NET gene has been identified [13]. The 5) flanking promoter region of the NET gene contains several important cis-elements for transcription [14].…”

Pharmacogenetics of antidepressant drugs: An update

“…NET is also a target for TCA, NET-selective reuptake inhibitors and psychostimulants, including cocaine, methylphenidate and amphetamine [105,106]. Moreover, NET mutations have been implicated in depression or in some other psychiatric disorders [107,108]. Several polymorphisms have been identified in the human NET gene such as rs5566, rs5563, rs5558, rs5569, rs36024 and rs2242446 variants which were proved to be functional and impact the effect of ADs [109,110].…”